Role of Ferroptosis – A Novel Programmed Cell Death in Temozolomide Therapy for Brain Cancer

TEMOZOLOMIDE- Role of Ferroptosis in Brain Cancer

Glioblastoma (GBM) are the most prevalent type of primary malignant brain tumor in adults that can develop in the brain stem, cerebellum, or spinal cord. Temozolomide (TMZ) is an alkylating agent that is used to treat adults with newly diagnosed GBM and resistant anaplastic astrocytoma who have progressed on a nitrosourea and procarbazine-containing therapy regimen. Ferroptosis, a novel form of programmed cell death, plays a crucial role in glioblastoma therapy. Cell membrane damage produced by mechanisms such as intracellular iron build-up, reactive oxygen species (ROS), lipid peroxidation, glutathione peroxidase (GPX) activity failure, and x-catenin (xCT) causes ferroptosis (iron dependent programmed cell death). This blog discusses the molecular mechanisms of ferroptosis, its application, and challenges in the development and treatment of glioblastoma. GBM invasiveness and treatment resistance may increase if ferroptosis is avoided due to changes in glucose, lipid, glutamine, and iron metabolism. Targeting ferroptosis, which involves fatal phospholipid peroxidation due to dysregulated redox homeostasis and cellular metabolism, could be a promising treatment for GBM, as it is essential for tumor cell viability.

PERTUZUMAB Advancing in HER2-Positive Breast Cancer

PERTUZUMAB ADVANCING IN HER2 POSITIVE BREAST CANCER

Breast cancer is a diverse disease with varying clinical presentations, morphologic features, and molecular characteristics. It is influenced by various genetic pathways and is a major trend in breast cancer care. Neoadjuvant chemotherapy is a major trend, requiring integrated multidisciplinary care from pathologists, radiologists, surgeons, and oncologists. Anti-HER2 therapy has improved clinical results for HER2-positive breast cancer patients.

Pertuzumab, a humanized monoclonal antibody, targets the extracellular dimerization domain of HER2, inhibiting downstream signaling and cell survival pathways. It is used in conjunction with trastuzumab and docetaxel to treat HER2-positive metastatic breast cancer. In addition to directly encouraging the death of cancer cells, monoclonal antibodies also trigger immunological activation, which is deadly to tumour cells.

Pertuzumab possesses the capability to elicit immune effector responses, including cell-mediated cytotoxicity that is dependent on antibodies. The antibody targets the PI3K/AKT and RAS/MEK/ERK pathways, protecting normal cells from suicide. It can activate immunological effector mechanisms, such as antibody-dependent cell-mediated cytotoxicity. Trastuzumab and pertuzumab function in complementary ways, highlighting the importance of understanding the biology of this devastating disease. This blog focuses on the mechanism of pertuzumab in patients with early-stage HER2-positive breast cancer receiving neoadjuvant treatment.

Current Scenario of Clinical Trials of Cell, Gene and RNA Therapies

Current Scenario of Clinical Trials of Cell, Gene and RNA Therapies

Constant emergence of new gene therapies as well as refinement of the existing ones changes the global landscape of the cell and gene therapies clinical trials, where the US, China, and Europe are leading in respect of the number of trials conducted. As per Global Data, China showed 15% faster growth in cell and gene therapy clinical trials making the Asia-Pacific region contributes for one-third of the trial activities. As a result, the Asia Pacific region is witnessing 50% faster growth than the rest of the world (ROW). Asia Pacific region leads globally in terms of CAR-T cell gene therapy clinical trials for the time period 2015-2022 since China alone conducted ~60% of all CAR-T trials. Till April 2022, there are 19 approved gene therapies, 17 RNA-approved therapies while 56 non-genetically modified approved cell therapies (Figure 1). Details of the approved location of the clinical trials of gene therapies and RNA therapies drug product are provided in Table No.1 and Table No. 2 respectively, which presents a bird’s-eye view of the landscape of the clinical trials of the approved gene and RNA therapies.

Engineered Nanoparticles for the Delivery of Anticancer Therapeutics

Engineered Nanoparticles for the Delivery of Anticancer Therapeutics

Therapeutic agents in cancer treatment are aimed at rapidly dividing cells, limiting their multiplication, and promoting apoptosis. The lack of selectivity of these conventional methods resulted in needless damage to normal cells leading to severe adverse effects. Nanotechnology in medicine gratifies the constraint in conventional treatment by delivering conventional drugs to the targeted tissue or organ and plays an important role in targeting the delivery, thereby avoiding systemic toxicity and increasing the bioavailability and therapeutic index of the drug. The advantage of using nanoparticles as drug carriers are in their binding competence and reversing multidrug resistance. Using active and passive targeting strategies, nanoparticles enhance intracellular drug concentrations. The present review focuses the on the basic pathophysiology of cancer and the various types of nanoparticulate drug delivery systems that have been explored so far, taking advantage of the tumor vasculature and other molecular mechanisms which differentiates cancer cells from normal ones, for the delivery of anticancer therapeutics for effective management of cancer. The article also aims to focus on the various surface-engineered nanoparticles for the targeted delivery of cancer.